Grant: Operating Grant

Innate immunity is an ancient system of host defense that predates the adaptive immune system and is conserved in almost all multicellular organisms from insects to mammals. Innate immunity relies on a set of protein receptors that are strategically expressed in cells that are likely to encounter pathogens such as bacteria and viruses, early on in an infection. The interaction of these receptors with components from the pathogen, propagates a signal into the cell that leads to changes in gene expression and accompanying responses by the host that work to eliminate the pathogen. This research proposal aims to elucidate the atomic level details for host-pathogen interactions in three important families of proteins that mediate innate immunity: 1) IFIT proteins, 2) NOD proteins and 3) SMPDs. NODs are receptors within the cell that sense the presence of invading bacteria. IFITs are response proteins that help eliminate viral infections. SMPDs are important for returning the immune response off once it has completed its task. Understanding the molecular details of how these proteins fulfill their cellular roles in defending the host from unwanted pathogens will be an important step towards the development of therapeutic drugs in diseases like cancer and autoimmune disorders, as well as several infectious and inflammatory diseases.